title: Dysregulation of brain olfactory and taste receptors in AD, PSP and CJD, and AD-related model.
abstract: Recently, we have shown the expression of novel chemoreceptors corresponding to the olfactory receptor (OR) and taste receptor (TASR) families in the human brain. We have also shown dysregulation of ORs and TASRs in the cerebral cortex in Parkinson's disease. The present study demonstrates the presence of OR mRNA and mRNA of obligated downstream components of OR signaling adenylyl cyclase 3 (ADYLC3) and olfactory G protein (Gnal) in the cerebral cortex of the mouse. Dysregulation of selected ORs and TASRs has been found in the entorhinal cortex and frontal cortex in Alzheimer's disease (AD) in a gradient compatible with Braak and Braak staging; frontal cortex in terminal stages of Progressive Supranuclear Palsy; and frontal cortex and cerebellum in Creutzfeldt-Jakob disease subtypes methionine/methionine at codón 129 of PRNP (MM1) and valine/valine at codón 129 of PRNP (VV2). Altered OR, ADYLC3 and Gnal mRNA expression with disease progression has also been found in APP/PS1 transgenic mice, used as a model of AD. The function of these orphan receptors is not known, but probably related to cell signaling pathways responding to unidentified ligands. Variability in the drift, either down- or up-regulation, of dysregulated genes, suggests that central ORs and TASRs are vulnerable to variegated neurodegenerative diseases with cortical involvement, and that altered expression of ORs and TASRs is not a mere reflection of neuronal loss but rather a modulated pathological response.
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital-IDIBELL, Hospitalet de Llobregat, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Ansoleaga
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital-IDIBELL, Hospitalet de Llobregat, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Garcia-Esparcia
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital-IDIBELL, Hospitalet de Llobregat, Spain; CIBERNED (Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas), Spain.
authors.forename: F
authors.initials: F
authors.lastname: Llorens
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital-IDIBELL, Hospitalet de Llobregat, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital-IDIBELL, Hospitalet de Llobregat, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Aso
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital-IDIBELL, Hospitalet de Llobregat, Spain; University of Barcelona, Hospitalet de Llobregat, Spain; CIBERNED (Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas), Spain. Electronic address: 8082ifa@gmail.com.
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005625:Frontal Lobe / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000473:pathology; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018035:Receptors, Odorant / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013494:Supranuclear Palsy, Progressive / Q000235:genetics*; D013649:Taste; D015854:Up-Regulation
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018035:Receptors, Odorant; C084618:olfactory G protein subunit alpha olf; D000262:Adenylyl Cyclases
keywords: APP/PS1 transgenic mice; Alzheimer; Creutzfeldt–Jakob disease; Progressive Supranuclear Palsy; olfactory receptors; taste receptors